Fatty acid binding protein 4 regulates pancreatic cancer cell proliferation via activation of nuclear factor E2-related factor 2

• Published in: Surgery for obesity and related diseases Vol. 18; no. 4; pp. 485 - 493
• Main Authors: Wirth, Keith, Shinoda, Shuhei, Sato-Dahlman, Mizuho, Dickey, Deborah M., Bernlohr, David A., Ikramuddin, Sayeed, Yamamoto, Masato
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2022
• Subjects: Animals; Cell Proliferation; FABP4; Fatty acid binding protein 4; Fatty Acid-Binding Proteins - genetics; Fatty Acid-Binding Proteins - metabolism; Humans; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; NRF2; Pancreatic cancer; Pancreatic Neoplasms; Cell proliferation; FABP4; Fatty acid binding protein 4; NRF2; Pancreatic cancer
• ISSN: 1550-7289; 1878-7533
• DOI: 10.1016/j.soard.2021.12.002

Obesity and diabetes are associated with an increased incidence of pancreatic cancer. Fatty acid binding protein 4 (FABP4), noted to be higher in patients with severe obesity, is linked to the development and progression of several cancers, and its level in the circulation decreases after bariatric surgery. In this paper, we evaluate the role of FABP4 in pancreatic cancer progression. University Hospital and Laboratories, United States. When Panc-1 (human) and Pan02 (mouse) pancreatic cancer cells were treated with FABP4 or the-single-point mutant FABP4 (R126Q, fatty acid binding site mutant), only FABP4 stimulated cellular proliferation. The transcriptional activity of nuclear factor E2-related factor 2 (NRF2) was increased in response to FABP4 but not the R126Q. FABP4 treatment also led to downregulation of reactive oxygen species (ROS) activity. Consistent with induced cell propagation by FABP4, the growth of Pan02 tumor was decreased in FABP4-null animals compared with C57BL/6J controls. These results suggest that FABP4 increases pancreatic cancer proliferation via activation of NRF2 and downregulation of ROS activity. FABP4 stimulated cellular proliferation.Nuclear factor E2-related factor 2 (NRF2) was increased in response to FABP4.The tumor growth was decreased in FABP4 null animals compared to controls.FABP4 increases pancreatic cancer proliferation via activation of Nrf2.